Overexpression of Eph transcripts has been observed in some carcinomas of the colon, lung, and liver. Eph is the largest family of receptor tyrosine kinases and most of the family members are expressed primarily, but not exclusively, in the nervous system. A cDNA was isolated that encodes Xek (Xenopus Elk-like Kinase), a tyrosine kinase receptor that appears to be ubiquitously expressed in adult tissues with higher expression observed in brain and ovary. In situ hybridization analysis demonstrates localized mRNA expression in the brain, branchial arches, trigeminal facial ganglion, and the post-mitotic retina cells of the swimming tadpole stage of development. Xek is an amphibian member of the Eph family, and may play a role in the development or function of the central nervous system. Recent studies have begun to identify ligands that can bind or activate members of the Eph family of receptor tyrosine kinases. These ligands described thus far are all membrane bound. Functional roles for the receptor-ligand interactions are beginning to be determined and suggest that they participate in axon bundling and guidance. We have isolated a cDNA encoding a putative ligand, termed Xlerk (Xenopus Ligand for Eph Receptor Kinases), that shows close homology with rat Lerk2 and has a very highly conserved intracellular domain. While there was some overlap in the expression pattern of the Xek receptor when compared to Xlerk, there also appears to be significant differences. Xlerk transcripts were observed in the olfactory placode, olfactory bulb, developing somites and innervations of the heart and gut (myenteric plexus). We have found that ectopic expression of Xlerk in the developing embryo causes the blastomeres of the embryo to disaggregate, suggesting a possible role in cell adhesion.